A crucial component in the recent major advances in genomics research has been the uniting of advances in computers, informatics, and networking with those in biology. As genome sequencing throughput has increased, the technological burden has shifted increasingly to analysis and informatics. This project was established ensure that the necessary computational tools and resources are available to the NIH community. Several computational resources are maintained and operated for the NIH intramural community. These include a SYBASE database server for design and development of genomic databases; a Perkin Elmer ABD Inherit FDF server system supporting Macintosh client software throughout the NIH for assembly and analysis of sequence data; support for a large number of sequence analysis programs available through the DCRT Advanced Laboratory Work-station project. Project staff serve as primary DCRT consultants for problem resolution as it pertains to the areas of genomics and sequence analysis. In collaboration with Dr. Louis Staudt, NCI/MB, a Sequence Profile Analysis (SPA) system for managing, screening and characterizing large numbers of sequence data has been developed. This system is currently used to filter EST sequences for cDNA microarray based gene expression analysis. A relational database schema was designed and implemented in a SYBASE 11 database. Software tools were identified, developed and integrated into the system to automate analysis procedures including remote retrieval of data, BLAST homology searching and clustering. Access to the database is provided through a web site designed and developed using Java JDBC/SYBASE jConnect. Approximately 20,000 sequences, representing approximately 10,000 clones from the Germinal Center Cell cDNA library have been analyzed with the system. Based on the researchers criteria, over 1000 clones have been identified as novel genes or genes which are lymphoid specific. Computational genetic linkage analysis is a popular method for researchers to discover the likeliest chromosomal locations for inherited disease genes. In close collaboration with Dr. Alejandro Schaffer (principle author of FASTLINK), NHGRI, linkage programs have been installed, tested and made available on a range of DCRT computing resources from ALW work stations to the SP2 parallel computing system. Computing procedures and tools have been designed and implemented to solve common problems among NIH researchers performing linkage analysis. Close, direct personal customer support was provided to a number NIH researchers, successfully assisting them in this complex task. A Linkage Analysis Web site has been setup and serves as a focal point for information specifically applicable to NIH. We continue to explore ways to provide computational resources through Web based technologies, including HTML, CGI bin programs and Java applets. Web access to an HLA peptide binding prediction application, a promoter scan application and a sequence signal scan have been developed and are available. Evaluation and Planning for the local mirroring of several Web sites, including the Biology Workbench Web site designed by the Dr. Shankar Subramaniam's computational biology group at the NCSA (Beckman Institute, Urbana, Illinois) and the WIT2 site designed by Dr. Ross Overbeek, Argonne National Laboratory are in progress.